4School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia

Abstract

Objective: Medium-chain fatty acids (MCFA) have been reported to be less obesogenic than long-chain fatty acids (LCFA), however relatively
little is known regarding their effect on insulin action. Here we examined the tissue-specific effects of MCFA on lipid metabolism
and insulin action.

Methods: C57BL6/J mice and Wistar rats were fed either a low-fat (LF) control diet or high-fat diets rich in MCFA or LCFA for 4-5
weeks and markers of mitochondrial oxidative capacity, lipid levels and insulin action were measured.

Results: Mice fed the MCFA diet displayed reduced adiposity and better glucose tolerance than LCFA-fed animals. In skeletal muscle,
triglyceride levels were increased by the LCFA diet (77%, P<0.01), but remained at LF control levels in the MCFA-fed animals.
The LCFA-diet increased (20-50%, P<0.05) markers of mitochondrial metabolism in muscle compared to LF controls, however the
increase in oxidative capacity was substantially greater in MCFA-fed animals (50-140% vs. LF controls, P<0.01). The MCFA diet
induced a greater accumulation of liver triglycerides than the LCFA diet, likely due to an upregulation of several lipogenic
enzymes. In rats, isocaloric feeding of MCFA or LCFA HF diets induced hepatic insulin resistance to a similar degree, however
insulin action was preserved at the level of LF controls in muscle and adipose from MCFA-fed animals.

Conclusions: MCFA reduce adiposity and preserve insulin action in muscle and adipose, despite inducing steatosis and insulin resistance
in the liver. Dietary supplementation with MCFA may therefore be beneficial for preventing obesity and peripheral insulin
resistance.